Anthony J. Comerota

Results of a prospective, randomized trial of surgery versus thrombolysis for occluded lower extremity bypass grafts.

PURPOSEnThe purpose of this study was to prospectively evaluate the treatment of patients with occluded lower extremity bypass grafts, comparing surgical revascularization with catheter-directed thrombolysis.nnnMATERIALS AND METHODSnOne hundred twenty-four patients (68% male and 32% female) with lower limb bypass graft occlusion (46 autogenous and 78 prosthetic) were prospectively randomized to surgery (n = 46) or intra-arterial catheter-directed thrombolysis (n = 78) with recombinant tissue plasminogen activator (rt-PA) 0.1 mg/kg/h modified to 0.05 mg/kg/h for up to 12 hours, or urokinase (UK) 250,000 U bolus followed by 4,000 U/min for 4 hours, then 2,000 U/min for up to 36 hours. A composite clinical outcome including death, amputation, ongoing/recurrent ischemia, and major morbidity was analyzed on an intent-to-treat basis at 30 days and 1 year.nnnRESULTSnThe average duration of graft occlusion was 34.0 days, with 58 (48%) presenting with acute ischemia (0 to 14 days) and 64 (52%) with chronic ischemia (> 14 days). Thirty-nine percent randomized to lysis failed catheter placement and required surgical revascularization. Overall, there was a better composite clinical outcome at 30 days (P = 0.023) and 1 year (P = 0.04) in the surgical group compared with lysis, due predominately to a reduction in ongoing/recurrent ischemia, most notable in autogenous grafts. However, following successful catheter placement, patency was restored by lysis in 84%, and 42% had a major reduction in their planned operation. One-year results of successful lysis compared favorably with the best surgical procedure, which was new graft placement. Acutely ischemic patients (0 to 14 days) randomized to lysis demonstrated a trend toward a lower major amputation rate at 30 days (P = 0.074) and significantly at 1 year (P = 0.026) compared with surgical patients, while those with > 14 days ischemia showed no difference in limb salvage but higher ongoing/recurrent ischemia in lytic patients (P < 0.001). Patients with occluded prosthetic grafts had greater major morbidity than did those with occluded autogenous grafts (P < 0.02).nnnCONCLUSIONSnProper catheter positioning currently limits the potential of catheter-directed thrombolysis for lower extremity bypass graft occlusion. Patients with graft occlusion > 14 days have a significantly better outcome when treated surgically, with a new bypass being the best surgical option. However, in patients with acute limb ischemia (< 14 days) successful thrombolysis of occluded lower extremity bypass grafts improves limb salvage and reduces the magnitude of the planned surgical procedure. Patients with occluded prosthetic grafts suffer more major morbid events compared with occluded autogenous grafts.

Adventitial elastolysis is a primary event in aneurysm formation

PURPOSEnAdventitial elastin degradation is a hallmark of abdominal aortic aneurysm (AAA) formation in human beings, although the quantitative relationship between elastin loss and AAA formation and growth is unknown. This study was undertaken to quantitate the reduction of adventitial elastin for small AAA, to determine whether the loss of this structural component parallels aneurysm growth, and to examine the ultrastructure of the remaining elastin elements.nnnMETHODSnLongitudinal strips of anterior aneurysm wall were taken from 12 patients having elective repair of small (diameter < 5 cm, n = 4), moderate (diameter < 5 to 7 cm, n = 4), or large (diameter > 7 cm, n = 4) AAA and from six normal control subjects at autopsy. Specimens were prepared with elastin and collagen stains for histologic examination or formic acid for scanning electron microscopic evaluation of elastin architecture. Adventitial elastin content of aneurysmal and control aortas was quantitated with video microscopy and compared by aneurysm diameter.nnnRESULTSnThe inner portion of adventitia of normal aortic wall was composed of densely compacted alternating lamellae of elastin and collagen, which were grossly disrupted in all aneurysms. The remaining elastin fibers were disorganized and tortuous. There was an 81.6% +/- 2.1% reduction in elastin lamellae and an 85.7% +/- 4.2% reduction in fibers per lamellae compared with the number in control aortas (p < 0.001). Size of the aneurysm made no difference in adventitial elastin content.nnnCONCLUSIONnThese data strongly suggest that elastolysis is a primary event in AAA formation that occurs before over loss of adventitial structural integrity and the development of small aneurysms.

Popliteal venous aneurysm: Report of two cases and review of the world literature

Two new cases of popliteal venous aneurysm are reported and added to the 22 other cases of popliteal venous aneurysm available for review. Both patients were first seen with acute pulmonary embolism and were treated with thrombolytic therapy followed by anticoagulation. Each had recurrent venous thromboembolism before discovery of the popliteal venous aneurysm. One popliteal venous aneurysm was diagnosed with phlebography and the second with venous duplex imaging, confirmed with phlebography. Both were surgically corrected with tangential aneurysmectomy and lateral venorrhaphy. Twenty-four cases of popliteal venous aneurysm are now available for review. Seventy-one percent (17 of 24) presented with pulmonary embolism, 88% (21 of 24) were saccular, and 96% (23 of 24) were located in the proximal popliteal vein. All but two were diagnosed by ascending phlebography. Three patients received no treatment: in two of these the outcome was not documented and the third had occasional pain. Two patients received anticoagulation without subsequent operative repair and both died of recurrent pulmonary emboli. Operative correction resulted in a 75% patency rate with 21% complications, most of which were related to postoperative anticoagulation. No patient who was operated on had subsequent pulmonary embolism, and there were no operative deaths. We suggest that all patients who have pulmonary embolism have lower-extremity venous duplex imaging. All popliteal venous aneurysms should be surgically repaired, inasmuch as nonoperative therapy results in recurrent thromboembolism and an unacceptably high mortality rate. Tangential aneurysmectomy with lateral venorrhaphy is the recommended procedure.

Hemodynamic deterioration in chronic venous disease

Clinical deterioration of patients with chronic venous disease (CVD) has been well described and a standardized classification has been proposed. The progressive hemodynamic deterioration producing these clinical findings is less well appreciated. This study examines and correlates venous hemodynamics with clinical severity in patients with CVD. Two hundred seventy-four extremities from 149 patients with varying degrees of CVD and 56 extremities from 28 symptom-free volunteers were evaluated clinically and hemodynamically. Each limb was assessed for functional venous volume, degree of valvular insufficiency, efficiency of the calf muscle pump, and noninvasive estimate of ambulatory venous pressure. In addition, exercise venous pressures were recorded in 56 extremities from 36 patients and 9 extremities from 6 volunteers. As CVD progresses from class 0 to class 2, venous volume expands, valvular function deteriorates, the calf muscle pump becomes inefficient, and ambulatory venous hypertension develops. However, once extremities develop brawny edema or hyperpigmentation, further deterioration of limb hemodynamics does not occur. Patients with deep venous obstruction have more severe valvular insufficiency, calf muscle pump dysfunction, and ambulatory venous hypertension than have patients without evidence of obstruction. Residual volume fraction offers a reliable noninvasive estimate of ambulatory venous pressure (r = 0.76), although its correlation was significantly better for patients without venous obstruction (r = 0.86) than for those with obstruction (r = 0.40; p < 0.05). Deterioration in venous hemodynamics parallels clinical severity through class 2. Once brawny edema and hyperpigmentation occur, ulceration develops without additional deterioration of venous hemodynamics.

The CAPTURE registry - Analysis of strokes resulting from carotid artery stenting in the post approval setting: Timing, location, severity, and type

Background:Although previous reports of carotid stenting with embolic protection (CAS) have focused on clinical outcomes of death, stroke and myocardial infarction, there are few data available characterizing the strokes that occur during CAS, thus limiting understanding of potential mechanisms. This report examines the timing, location, severity, and type of strokes occurring with CAS in the Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Unanticipated or Rare Events (CAPTURE) study. Methods:CAPTURE is a prospective, multicenter registry conducted to assess outcomes of CAS in the postapproval setting after device approval. A neurologist examined the patients before the procedure, at 24 hours and 30 days post-procedure. The primary end point was a composite of death, any stroke, or myocardial infarction within 30 days post-procedure. Strokes and all neurologic events suspected to be strokes were adjudicated by an independent Clinical Events Adjudication Committee using prespecified definitions. Source documents of all patients with strokes in this cohort were reviewed. Results:The 30-day results were available for 3500 patients. The 30-day primary end point event rate of death, stroke, and myocardial infarction was 6.3% (95% confidence interval: 5.5%–7.1%), and the rate of major stroke and death was 2.9% (95% confidence interval: 2.4 to 3.5). 4.8% of patients experienced a stroke (3.9% ipsilateral and 0.9% nonipsilateral, 2% major). A majority of stroke symptoms (57.7%) were noted post-procedure and pre-discharge, whereas 22.3% were noted during the procedure and 20% postdischarge. A similar timing distribution regardless of preprocedural symptomatic status was found. Overall, 41% (69 of 170) of all strokes were major. The incidence of major strokes was statistically significantly greater among symptomatic compared with asymptomatic patients, 4.6% (22 of 482) and 1.6% (47 of 3018), respectively. There were more minor than major strokes in asymptomatic patients (63% vs. 37%; P = 0.10), whereas stroke severity was equally distributed in symptomatic patients. Among the ipsilateral strokes, almost half (44%) were major, whereas only one-quarter (26%) of the nonipsilateral strokes were major. Overall, 23% of the major strokes were hemorrhagic and 94% of these strokes were noted on the ipsilateral side. There was a tendency toward more major hemorrhagic strokes in symptomatic than in asymptomatic patients (36% vs. 17%; P = 0.07). Fifty-four percent of the strokes post-procedure and pre-discharge were major, whereas 27% of the strokes postdischarge were major. Furthermore, 65% of hemorrhagic strokes were noted post-procedure and pre-discharge, 30% postdischarge. Conclusions:Strokes related to CAS seem to become clinically apparent after the procedure but before discharge in the majority of events. Nevertheless, a significant minority of stroke symptoms follows discharge from the hospital, typically after 24 hours. Timing of stroke after CAS seems to be similar to timing of stroke after carotid endarterectomy. Moreover, nearly 1 in 5 strokes occur in a nonipsilateral distribution, with the exception of intraprocedural events, which were all ipsilateral to the stent being implanted. Hemorrhagic stroke seemed to be more prevalent in the strokes occurring in the post-procedure period. These descriptors of stroke severity, location, and timing may provide insight in to the mechanistic causes of adverse neurologic outcomes in CAS.

Venous duplex imaging: Should it replace hemodynamic tests for deep venous thrombosis?***

Noninvasive diagnosis of deep venous thrombosis has traditionally relied on detection of alterations in venous hemodynamics. Although phleborheography is among the most sensitive tests, it is inadequate for diagnosing infrapopliteal and nonocclusive proximal thrombi and for surveillance of patients at high risk for deep venous thrombosis. Venous duplex imaging is a new technique being rapidly accepted, however, without the same critical analysis given to previous diagnostic modalities. The purpose of this study is to evaluate the diagnostic acumen of venous duplex imaging compared to phleborheography and ascending phlebography in two distinct patient groups, and to determine whether patient selection, and thus the location or magnitude of thrombi have significant influence on these diagnostic tests. One hundred ten extremities in 103 patients were prospectively evaluated with venous duplex imaging, phleborheography, and ascending phlebography within the same 24-hour period. Patients were categorized into one of two groups: Diagnostic--patients evaluated because of clinical suspicion of acute deep venous thrombosis; and Surveillance--patients at high risk of postoperative deep venous thrombosis after total joint replacement, but not symptomatic. Patients in the diagnostic group had a greater frequency of deep venous thrombosis (p less than 0.001) and significantly more occluding above-knee thrombi (p = 0.054) compared to those in the surveillance group. Phleborheography detected 73% (27/37) of above-knee thrombi in the diagnostic group compared to 29% (2/7) in the surveillance group (p = 0.036). This difference was not noted with venous duplex imaging, which detected 100% of above-knee thrombi in both diagnostic and surveillance groups and 78% (7/9) of all below-knee thrombi.(ABSTRACT TRUNCATED AT 250 WORDS)

The preoperative diagnosis of the ulcerated carotid atheroma

Arteriography and carotid duplex imaging accurately quantify the degree of stenosis caused by carotid atheroma. Since arteriography is inconsistent in identifying carotid ulceration, and controversy exists regarding the diagnostic accuracy of carotid B-mode imaging, a prospective study was performed comparing the two techniques to 126 carotid endarterectomy specimens. Sixty percent (76/126) of specimens contained ulcers. The diagnostic sensitivity for B-mode imaging and arteriography was 47% (36/76) and 53% (40/76), respectively (p = NS). Importantly, the degree of stenosis caused by the plaque significantly affected diagnostic sensitivities. B-mode sensitivity was 77% (10/13) in plaques less than or equal to 50% and 41% (26/63) for plaques greater than 50% (p = 0.03). Arteriography likewise detected 77% (10/13) of ulcers in plaques less than or equal to 50% stenosis and 48% (30/63) in plaques with greater than 50% stenosis (p = 0.07). In patients with focal symptoms, 100% (10/10) of plaques with less than or equal to 50% stenosis contained ulcers, whereas in plaques with greater than 50% stenosis 63% (36/57) contained ulcers (p = 0.02). These data indicate that the diagnostic sensitivity for carotid ulceration is not significantly different between B-mode carotid imaging and arteriography. Since most B-mode errors occur with high-grade stenoses this short-coming is unlikely to adversely affect patient care. Previous studies investigating the ability of carotid B-mode imaging to detect ulceration failed to address quantitative aspects of the carotid plaque. These data appear to resolve the previously existing controversy.

Intermittent claudication: magnitude of the problem, patient evaluation, and therapeutic strategies.

Intermittent claudication (IC), the symptom of exercise-induced muscle ischemia of peripheral arterial disease (PAD), afflicts and limits the activities of a significant number of patients. Incidence and prevalence of IC depends on the population studied and the diagnostic instruments used. In large studies, prevalence has ranged from 3% to 10%, with a sharp increase in those aged > or =70 years. Over the next 20 years, the total number of patients affected is expected to increase significantly due to anticipated demographic changes. Analysis of the natural history of IC demonstrates that the risk of cardiovascular morbidity and mortality far exceeds that of severe limb ischemia or limb loss. In fact, only 2% to 4% of all patients with IC will require a major amputation in their lifetime. However, life expectancy is approximately 10 years less than that of an age-matched cohort. By now, PAD is well recognized as a marker of systemic atherosclerosis. The cornerstone of patient evaluation is a history and physical examination, including a detailed atherosclerotic risk-factor assessment. In the differential diagnosis of IC, clinicians should consider etiologies such as arthritis, spinal stenosis, radiculopathy, venous claudication, or inflammatory processes. In >80% of all patients, it is possible to locate the responsible arterial segment by combining the location and severity of pain with a pulse examination. Noninvasive diagnostic studies help determine the level of disease, may unmask a hemodynamically significant stenosis, and are useful in follow-up. Arteriography is reserved for patients in whom the decision for revascularization has been made. Knowing the anatomic detail of a lesion allows the clinician to determine whether and what type of intervention is feasible. Standard therapy for all patients should be directed at both peripheral and systemic atherosclerosis, beginning with risk-factor modification in the form of smoking cessation, optimal diabetes control, and lipid normalization. The benefits of supervised exercise rehabilitation include significantly increased walking distance and enhanced quality of life. Platelet inhibition has been shown to reduce the risk of ischemic stroke, myocardial infarction, and vascular death and should be prescribed for all but those in whom it is medically contraindicated. Symptom-specific pharmacotherapy with a broad range of medications has yielded disappointing results in the past. However, recent studies have demonstrated that patients receiving the novel agent cilostazol experienced increases in walking distance and improvements in quality of life.

Intermittent calf and foot compression increases lower extremity blood flow.

PURPOSEnAlthough foot compression increases foot skin perfusion and calf compression increases popliteal artery blood flow, these compression techniques have not been evaluated in combination. The purpose of this study was to evaluate whether calf and foot compression applied separately and simultaneously increase popliteal artery blood flow and/or foot skin perfusion, and to assess the relative merits of compression in patients with superficial femoral artery occlusion.nnnMETHODSnTwenty-two legs from 12 normal volunteers with ankle/brachial indices (ABIs) > 0.96, and 10 legs from 7 claudicator patients with angiographically documented superficial femoral artery (SFA) occlusion and patent popliteal arteries with ABIs < 0.8 were studied in the sitting position. Calf and foot cuffs connected to a rapidly inflating and deflating timed-pressure pump (Art-Assist-AA 1000; ACI Medical Inc., San Marcos, California) were applied to the subject in the sitting position. Skin blood flow of the great toe was measured with a laser doppler (Laserflo model BPM 403A; TSI Inc., St. Paul, Minnesota), and popliteal artery blood flow was measured using duplex ultrasonography (ATL-Ultramark 9; Advanced Tech Laboratory, Bothell, Washington). Foot and calf compression was applied separately and simultaneously at 120 mm Hg pressure, with a 10-second inflation and 20-second deflation cycle. Popliteal artery blood flow and foot skin perfusion were recorded and the mean of 6 cycles calculated.nnnRESULTSnPrecompression popliteal artery blood flow (mL/min) for volunteers was 38.86 +/- 3.94, and for patients was 86.30 +/- 14.55 (P = 0.001). Precompression foot skin perfusion (mL/min/ 100/g tissue) for volunteers was 1.67 +/- 0.29, and for patients was 4.00 +/- 0.92 (P = 0.01). With the application of calf, foot, and simultaneous calf and foot compression, the popliteal artery blood flow increased in volunteers by 124%, 54%, and 173%, respectively, and in patients by 76%, 13%, and 50%. Foot skin perfusion increased in volunteers by 260%, 500%, and 328%, respectively, and in patients by 116%, 246%, and 188%. Relative increases in popliteal artery blood flow and foot skin perfusion were higher in volunteers compared with patients during compression; however, the absolute values for foot skin perfusion and popliteal artery blood flow were consistently higher in patients.nnnCONCLUSIONSnMeasured in the sitting position, the resting popliteal artery blood flow and foot skin perfusion are greater in patients with SFA occlusion compared with normal volunteers. Following compression, popliteal artery blood flow and foot skin perfusion increased in both groups, but relatively more in volunteers. Increases in popliteal artery blood flow are significantly higher with calf compression than with foot compression for both groups. A patent SFA allows for additive increases in popliteal artery blood flow with simultaneous foot and calf compression in normal persons, whereas this is not observed in patients. However, the increases in foot skin perfusion in patients with an occluded SFA parallel the increases shown in normal volunteers, with separate and simultaneous foot and calf compression.

Stump pressure, electroencephalographic changes, and the contralateral carotid artery: Another look at selective shunting

BACKGROUNDnSelective shunting during carotid endarterectomy is associated with the lowest operative stroke rate; therefore, patient selection for carotid shunting is critical. Electroencephalography (EEG) can detect ischemic brain cell dysfunction before irreversible injury. The carotid stump back pressure (CSP) has been inconsistent in determining the need for shunting, and contralateral carotid disease has had a variable impact. The purpose of this study was to evaluate CSP and operative EEG changes, and to determine the effect of contralateral carotid artery disease on determining the need for carotid shunting.nnnMETHODSnIn 140 consecutive carotid procedures, operative EEG and CSP were monitored, and contralateral carotid disease was documented. The carotid stump pressure/mean arterial pressure index (CSP/MAP) was also calculated to determine if this was a better indicator of the need for shunting than the CSP alone.nnnRESULTSnThere was a 58% incidence of EEG changes when the CSP was < or = 25 mm Hg, 32% with a CSP of 26 to 50 mm Hg, and 4% with a CSP > 50 mm Hg. There was a 43% incidence of EEG changes and lower CSP among patients with a contralateral occlusion, both of which were significantly different from patients with a patent contralateral carotid artery. Three patients with CSP > 50 mm Hg had EEG changes, but none had a contralateral occlusion. Two patients had permanent neurologic deficits, and 2 had transient deficits. Excluding combined procedures, operative stroke rate was 0.8%.nnnCONCLUSIONSnA CSP of < 50 mm Hg achieved a sensitivity of 89% in patients who developed ischemic EEG changes during carotid clamping, and a pressure > 50 mm Hg had a negative predictive value of 96%. However, a CSP of < 50 mm Hg had a positive predictive value of only 36%. Neither the addition of the status of the contralateral carotid artery or the calculation of the CSP/MAP improved the sensitivity of the CSP in determining the need for shunting. Operative EEG monitoring remains the most sensitive guide to carotid shunting in patients undergoing carotid endarterectomy under general anesthesia.